Magnetic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol micelles for docetaxel delivery in breast cancer: an in vitro study on two cell lines of breast cancer.

The aim of the present study was to load docetaxel (DCT) and Fe3O4 magnetic nanoparticles (MNPs) in polymeric micelles to concentrate them by an external magnetic field in target tissues. Oleic acid (OA) coated MNPs were prepared by hydrothermal method. The micelles were characterized for their zeta potential, particle size, drug loading and release efficacy. Fe loading efficacy was determined by atomic absorption. The magnetic micelles were characterized by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), transmission electron microscopy and vibrating sample magnetometer (VSM). The cytotoxicity of the micelles was studied by MTT assay on L929 fibroblast cells and also on two breast cancer cell lines of MCF-7 and MDA-MB-231. The optimum formulation showed 70% drug loading efficiency, zeta potential of -2.58 mV, particle size of 144.3 nm and drug release efficiency within 24 h of 68.9% at pH 5.5. Fe was loaded in these nanomicelles 290 µg/100 ml. TGA results confirmed the coating of MNPs with OA and polymeric micelles. The VSM analysis confirmed superparamagnetic property of the micelles. DCT loaded in micelles showed significantly more cytotoxicity compared to free drug on MCF-7 and MDA-MB-231 cells, but blank magnetic micelles had no significant cytotoxicity on normal fibroblast cells.

Linear and conformational B cell epitope prediction of the HER 2 ECD-subdomain III by in silico methods.

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases that play important roles in all processes of cell development. Their overexpression is related to many cancers, including examples in the breast, ovaries and stomach. Anticancer therapies targeting the HER2 receptor have shown promise, and monoclonal antibodies against subdomains II and IV of the HER2 extra-cellular domain (ECD), Pertuzumab and Herceptin, are currently used in treatments for some types of breast cancers. Since anti HER2 antibodies targeting distinct epitopes have different biological effects on cancer cells; in this research linear and conformational B cell epitopes of HER2 ECD, subdomain III, were identified by bioinformatics analyses using a combination of linear B cell epitope prediction web servers such as ABCpred, BCPREDs, Bepired, Bcepred and Elliprro. Then, Discotope, CBtope and SUPERFICIAL software tools were employed for conformational B cell epitope prediction. In contrast to previously reported epitopes of HER2 ECD we predicted conformational B cell epitopes P1C: 378-393 (PESFDGDPASNTAPLQ) and P2C: 500-510 (PEDECVGEGLA) by the integrated strategy and and P4: PESFDGD-X-TAPLQ; P5: PESFDGDP X TAPLQ; P6: ESFDGDP X NTAPLQP; P7: PESFDGDP-X-NTAPLQ; P8: ESFDG-XX-TAPLQPEQL and P9: ESFDGDP- X-NTAPLQP by SUPERFICIAL software. These epitopes could be further used as peptide antigens to actively immune mice for development of new monoclonal antibodies and peptide cancer vaccines that target different epitopes or structural domains of HER2 ECD.

Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin.

The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC(50) value of 15-fold lower than free etoposide.

Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design.

Amikacin as an aminoglycoside antibiotic was chosen to be loaded in a cholesterol carrier with nanoparticle size and sustained release profile to increase the dose interval of amikacin and reduce side-effects. To support the stability of solid lipid nanoparticles (SLNs), freeze-drying was suggested. Factors affecting the freeze-drying process in the present study included the type and concentration of cryoprotectants. Pre-freezing temperature effects were also studied on particle size of SLNs of amikacin. In some preliminary experiments, important factors which influenced the particle size of SLNs after lyophilization were selected and a D-optimal design was applied to optimize the freeze-drying conditions in the production of SLNs with minimum particle size growth after freeze-drying. Zeta potential, DSC thermograms, release profiles and morphology of the optimized particles were studied before and after freeze-drying. Results showed sucrose changed the particle size of SLNs of amikacin from 149 ± 4 nm to 23.9 ± 16.7 nm; in that situation, the absolute value of zeta potential changed from 1 ± 0.7 mV to 13 ± 4 mV. The release profiles showed a sustained release behavior of the loaded drug that did not change significantly before and after freeze-drying, but a burst effect was seen after it in the first 2 h. DSC analysis showed chemical interaction between amikacin and cholesterol.